This invention relates to oral dosage compositions, including a bilayer sustained release oral dosage composition containing a nasal decongestant, e.g., pseudoephedrine in one layer and the non-sedating antihistamine, desloratadine in a second layer and having less than about 2% of desloratadine degradation products in the compositions. The oral dosage compositions of this invention are useful for treating patients showing the signs and symptoms associated with allergic and/or inflammatory conditions such as the common cold, as well as signs and symptoms associated with allergic and/or inflammatory conditions of the skin such as dermatitis, and airway passages such as the upper respiratory disease conditions, perennial allergic rhinitis, seasonal allergic rhinitis and nasal congestion, allergic asthma, and nasal congestion.
Desloratadine, also called descarbethoxyloratadine, is disclosed in U.S. Pat. No. 4,659,716 as a non-sedating antihistamine useful as an anti-allergy agent. U.S. Pat. No. 5,595,997 discloses methods and compositions for treating seasonal allergic rhinitis symptoms using desloratadine.
U.S. Pat. Nos. 4,990,535 and 5,100,675 disclose a twice-a-day sustained release coated tablet wherein the tablet coating comprises descarbethoxyloratadine and a hydrophilic polymer and polyethylene glycol, and the tablet core comprises acetaminophen, pseudoephedrine or a salt thereof, a swellable hydrophilic polymer and pharmaceutically acceptable excipients.
U.S. Pat. No. 5,314,697 discloses an extended release tablet containing matrix core comprising pseudoephedrine sulfate and a coating comprising loratadine.
None of the prior art discloses the solid oral dosage compositions of this invention.
The successful development of a formulation of a desloratadine-pseudoephedrine twice-a-day and once-a-day products would be desirable, but would require (1) achieving a release rate profile for pseudoephedrine component over an extended period of about twelve hours or twenty four hours, respectively, while maintaining the safety and effectiveness of desloratadine, and (2) minimizing impurity formation due to the interaction between desloratadine and excipients in the pseudoephedrine layer that are incompatible with desloratadine.
It would be desirable for increased patient compliance to have a stable, extended release desloratadine-pseudoephedrine product substantially free of desloratadine impurities and additional polymorphic forms that is effective and safe when used on a twice-a-day or once-a-day basis for the treatment, management and/or mitigation of the signs and symptoms associated with the common cold, as well as allergic and/or inflammatory conditions of the skin or upper and lower airway passages such as seasonal and perennial allergic rhinitis and nasal congestion.
We have found that desloratadine discolors and decomposes in the presence of excipients disclosed in the prior art. We have discovered that these problems are substantially solved by (a) bilayer solid compositions of the present invention wherein immediate release layer contains desloratadine combined with a pharmaceutically acceptable carrier medium comprising a desloratadine protective amount of a pharmaceutically acceptable basic salt, and wherein the use of an acidic excipient in the immediate release layer is substantially avoided or (b) bilayer solid compositions of the present invention wherein a desloratadine-protective amount of at least one pharmaceutically acceptable antioxidant is present in at least one layer, and preferably, wherein two of said antioxidants are present in desloratadine-containing immediate release layer.
Thus, this invention provides a bilayer solid composition comprising (a) an immediate release first layer comprising an anti-allergic effective amount of desloratadine and at least one pharmaceutically acceptable excipient and (b) a sustained release second layer comprising an effective amount of a nasal decongestant and a pharmaceutically acceptable sustained release agent wherein the total amount of desloratadine decomposition products in the composition is less than, or equal to, about 2% by weight.